rs17228641

Variant names:

• chr15-32732607-G-A
• rs17228641
• NM_013372.7:c.*1362G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-32732607-G-A
• chr15-32732607-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013372.7(GREM1):​c.*1362G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 245,032 control chromosomes in the GnomAD database, including 765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.067 (428 hom., cov: 32)
  • Exomes 𝑓: 0.077 (337 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 6 publications found

Genes affected

GREM1 (HGNC:2001): (gremlin 1, DAN family BMP antagonist) This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GREM1 Gene-Disease associations (from GenCC):

• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P
• polyposis syndrome, hereditary mixed, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.*1362G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.*1362G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001355648.1
GREM1	NM_001191323.2	c.*1362G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.*1362G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.*1362G>A		3_prime_UTR_variant	Exon 2 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000652365.1	c.*1362G>A		3_prime_UTR_variant	Exon 2 of 2			ENSP00000498763.1
GREM1	ENST00000560830.1	c.*1362G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000453141.1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10142 AN: 152122 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.0765 AC: 7100 AN: 92792 Hom.: 337 Cov.: 0 AF XY: 0.0762 AC XY: 3274 AN XY: 42966

African (AFR) AF: 0.0226 AC: 85 AN: 3754

American (AMR) AF: 0.0600 AC: 144 AN: 2400

Ashkenazi Jewish (ASJ) AF: 0.0722 AC: 358 AN: 4956

East Asian (EAS) AF: 0.000182 AC: 2 AN: 10994

South Asian (SAS) AF: 0.0118 AC: 8 AN: 678

European-Finnish (FIN) AF: 0.0830 AC: 1225 AN: 14762

Middle Eastern (MID) AF: 0.0693 AC: 33 AN: 476

European-Non Finnish (NFE) AF: 0.0980 AC: 4723 AN: 48182

Other (OTH) AF: 0.0792 AC: 522 AN: 6590

GnomAD4 genome AF: 0.0666 AC: 10144 AN: 152240 Hom.: 428 Cov.: 32 AF XY: 0.0645 AC XY: 4802 AN XY: 74432

African (AFR) AF: 0.0200 AC: 833 AN: 41566

American (AMR) AF: 0.0701 AC: 1072 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4816

European-Finnish (FIN) AF: 0.0878 AC: 930 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6759 AN: 67994

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0875 Hom.: 917

Bravo AF: 0.0643

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17228641; hg19: chr15-33024808;